Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDRSHAZ)

• DOT Name: Gamma-adducin (ADD3)
• Synonyms: Adducin-like protein 70
• Gene Name: ADD3
• Related Disease:
  Cardiac disease
  Intellectual disability
  Neoplasm
  Nephropathy
  Adult glioblastoma
  Alzheimer disease
  Bipolar depression
  Bipolar disorder
  Cerebral palsy, spastic quadriplegic, 3
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  T-cell acute lymphoblastic leukaemia
  Cerebral palsy
  Complex neurodevelopmental disorder with motor features
  Spastic quadriplegic cerebral palsy
  Brain ischaemia
  High blood pressure
• UniProt ID: ADDG_HUMAN
• Pfam ID: PF00596
• Sequence:
  MSSDASQGVITTPPPPSMPHKERYFDRINENDPEYIRERNMSPDLRQDFNMMEQRKRVTQ
  ILQSPAFREDLECLIQEQMKKGHNPTGLLALQQIADYIMANSFSGFSSPPLSLGMVTPIN
  DLPGADTSSYVKGEKLTRCKLASLYRLVDLFGWAHLANTYISVRISKEQDHIIIIPRGLS
  FSEATASNLVKVNIIGEVVDQGSTNLKIDHTGFSPHAAIYSTRPDVKCVIHIHTLATAAV
  SSMKCGILPISQESLLLGDVAYYDYQGSLEEQEERIQLQKVLGPSCKVLVLRNHGVVALG
  ETLEEAFHYIFNVQLACEIQVQALAGAGGVDNLHVLDFQKYKAFTYTVAASGGGGVNMGS
  HQKWKVGEIEFEGLMRTLDNLGYRTGYAYRHPLIREKPRHKSDVEIPATVTAFSFEDDTV
  PLSPLKYMAQRQQREKTRWLNSPNTYMKVNVPEESRNGETSPRTKITWMKAEDSSKVSGG
  TPIKIEDPNQFVPLNTNPNEVLEKRNKIREQNRYDLKTAGPQSQLLAGIVVDKPPSTMQF
  EDDDHGPPAPPNPFSHLTEGELEEYKRTIERKQQGLEDAEQELLSDDASSVSQIQSQTQS
  PQNVPEKLEENHELFSKSFISMEVPVMVVNGKDDMHDVEDELAKRVSRLSTSTTIENIEI
  TIKSPEKIEEVLSPEGSPSKSPSKKKKKFRTPSFLKKNKKKEKVEA
• Function: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping. Binds to calmodulin (Probable). Involved in myogenic reactivity of the renal afferent arteriole (Af-art), renal interlobular arteries and middle cerebral artery (MCA) to increased perfusion pressure. Involved in regulation of potassium channels in the vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. Involved in regulation of glomerular capillary pressure, glomerular filtration rate (GFR) and glomerular nephrin expression in response to hypertension. Involved in renal blood flow (RBF) autoregulation. Plays a role in podocyte structure and function. Regulates globular monomer actin (G-actin) and filamentous polymer actin (F-actin) ratios in the primary podocytes affecting actin cytoskeleton organization. Regulates expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex and the primary podocytes. Regulates expression of nephrin in the glomeruli and in the primary podocytes, expression of nephrin and podocinin in the renal cortex, and expression of focal adhesion proteins integrin alpha-3 and integrin beta-1 in the glomeruli. Involved in cell migration and cell adhesion of podocytes, and in podocyte foot process effacement. Regulates expression of profibrotics markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E-cadherin, and mesenchymal markers vimentin and alpha-SMA. Promotes the growth of neurites.
• Tissue Specificity: .ubiquitously expressed.; Cleavage fragment 1-357 is abundantly expressed in the brain of patients with Alzheimer disease (AD), but hardly detectable in age-matched control individuals (at protein level).
• Reactome Pathway:
  RHOD GTPase cycle (R-HSA-9013405)
  RHOF GTPase cycle (R-HSA-9035034)
  Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac disease	DISVO1I5	Definitive	Biomarker	[1]
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Nephropathy	DISXWP4P	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Bipolar depression	DISA75FU	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Cerebral palsy, spastic quadriplegic, 3	DISFSPO5	Strong	Autosomal recessive	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[9]
Cerebral palsy	DIS82ODL	moderate	Genetic Variation	[6]
Complex neurodevelopmental disorder with motor features	DIS09FBL	Moderate	Autosomal recessive	[10]
Spastic quadriplegic cerebral palsy	DISBJRHC	Supportive	Autosomal recessive	[6]
Brain ischaemia	DIS9Q4RT	Limited	Biomarker	[11]
High blood pressure	DISY2OHH	Limited	Biomarker	[12]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Gamma-adducin (ADD3) affects the response to substance of Doxorubicin.	[34]
Fluorouracil	DMUM7HZ	Approved	Gamma-adducin (ADD3) affects the response to substance of Fluorouracil.	[34]
Paclitaxel	DMLB81S	Approved	Gamma-adducin (ADD3) affects the response to substance of Paclitaxel.	[34]
Topotecan	DMP6G8T	Approved	Gamma-adducin (ADD3) affects the response to substance of Topotecan.	[34]
Vinblastine	DM5TVS3	Approved	Gamma-adducin (ADD3) affects the response to substance of Vinblastine.	[34]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Gamma-adducin (ADD3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Gamma-adducin (ADD3).	[29]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Gamma-adducin (ADD3).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gamma-adducin (ADD3).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Gamma-adducin (ADD3).	[31]

18 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Gamma-adducin (ADD3).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Gamma-adducin (ADD3).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Gamma-adducin (ADD3).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Gamma-adducin (ADD3).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Gamma-adducin (ADD3).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Gamma-adducin (ADD3).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gamma-adducin (ADD3).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Gamma-adducin (ADD3).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Gamma-adducin (ADD3).	[22]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Gamma-adducin (ADD3).	[23]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Gamma-adducin (ADD3).	[24]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Gamma-adducin (ADD3).	[25]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Gamma-adducin (ADD3).	[26]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Gamma-adducin (ADD3).	[27]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Gamma-adducin (ADD3).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Gamma-adducin (ADD3).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Gamma-adducin (ADD3).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Gamma-adducin (ADD3).	[33]

References

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